Retinal Phenotyping of a Murine Model of Lafora Disease

Overview

Journal Genes (Basel)

Publisher MDPI

Date 2023 Apr 28

PMID 37107612

Authors

Ajoy Vincent

Kashif Ahmed

Rowaida Hussein

Zorana Berberovic

Anupreet Tumber

Xiaochu Zhao

Berge A Minassian

Affiliations

Soon will be listed here.

Abstract

Lafora disease (LD) is a progressive neurologic disorder caused by biallelic pathogenic variants in or , leading to tissue accumulation of polyglucosan aggregates termed Lafora bodies (LBs). This study aimed to characterize the retinal phenotype in mice by examining knockout (KO; ) and control (WT) littermates at two time points (10 and 14 months, respectively). In vivo exams included electroretinogram (ERG) testing, optical coherence tomography (OCT) and retinal photography. Ex vivo retinal testing included Periodic acid Schiff Diastase (PASD) staining, followed by imaging to assess and quantify LB deposition. There was no significant difference in any dark-adapted or light-adapted ERG parameters between KO and WT mice. The total retinal thickness was comparable between the groups and the retinal appearance was normal in both groups. On PASD staining, LBs were observed in KO mice within the inner and outer plexiform layers and in the inner nuclear layer. The average number of LBs within the inner plexiform layer in KO mice were 1743 ± 533 and 2615 ± 915 per mm, at 10 and 14 months, respectively. This is the first study to characterize the retinal phenotype in an mouse model, demonstrating significant LB deposition in the bipolar cell nuclear layer and its synapses. This finding may be used to monitor the efficacy of experimental treatments in mouse models.

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